We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Few studies have examined the genetic population structure of vector-borne microparasites in wildlife, making it unclear how much these systems can reveal about the movement of their associated hosts. This study examined the complex host–vector–microbe interactions in a system of bats, wingless ectoparasitic bat flies (Nycteribiidae), vector-borne microparasitic bacteria (Bartonella) and bacterial endosymbionts of flies (Enterobacterales) across an island chain in the Gulf of Guinea, West Africa. Limited population structure was found in bat flies and Enterobacterales symbionts compared to that of their hosts. Significant isolation by distance was observed in the dissimilarity of Bartonella communities detected in flies from sampled populations of Eidolon helvum bats. These patterns indicate that, while genetic dispersal of bats between islands is limited, some non-reproductive movements may lead to the dispersal of ectoparasites and associated microbes. This study deepens our knowledge of the phylogeography of African fruit bats, their ectoparasites and associated bacteria. The results presented could inform models of pathogen transmission in these bat populations and increase our theoretical understanding of community ecology in host–microbe systems.
The use of peritoneal catheters for prophylactic dialysis or drainage to prevent fluid overload after neonatal cardiac surgery is common in some centres; however, the multi-centre variability and details of peritoneal catheter use are not well described.
Methods:
Twenty-two-centre NEonatal and Pediatric Heart Renal Outcomes Network (NEPHRON) study to describe multi-centre peritoneal catheter use after STAT category 3–5 neonatal cardiac surgery using cardiopulmonary bypass. Patient characteristics and acute kidney injury/fluid outcomes for six post-operative days are described among three cohorts: peritoneal catheter with dialysis, peritoneal catheter with passive drainage, and no peritoneal catheter.
Results:
Of 1490 neonates, 471 (32%) had an intraoperative peritoneal catheter placed; 177 (12%) received prophylactic dialysis and 294 (20%) received passive drainage. Sixteen (73%) centres used peritoneal catheter at some frequency, including six centres in >50% of neonates. Four centres utilised prophylactic peritoneal dialysis. Time to post-operative dialysis initiation was 3 hours [1, 5] with the duration of 56 hours [37, 90]; passive drainage cohort drained for 92 hours [64, 163]. Peritoneal catheter were more common among patients receiving pre-operative mechanical ventilation, single ventricle physiology, and higher complexity surgery. There was no association with adverse events. Serum creatinine and daily fluid balance were not clinically different on any post-operative day. Mortality was similar.
Conclusions:
In neonates undergoing complex cardiac surgery, peritoneal catheter use is not rare, with substantial variability among centres. Peritoneal catheters are used more commonly with higher surgical complexity. Adverse event rates, including mortality, are not different with peritoneal catheter use. Fluid overload and creatinine-based acute kidney injury rates are not different in peritoneal catheter cohorts.
Major depressive disorder (MDD) is a highly prevalent psychiatric condition, yet many patients do not receive adequate treatment. Novel and highly scalable interventions such as internet-based cognitive-behavioral-therapy (iCBT) may help to address this treatment gap. Anhedonia, a hallmark symptom of MDD that refers to diminished interest and ability to experience pleasure, has been associated with reduced reactivity in a neural reward circuit that includes medial prefrontal and striatal brain regions. Whether iCBT can reduce anhedonia severity in MDD patients, and whether these therapeutic effects are accompanied by enhanced reward circuit reactivity has yet to be examined.
Methods
Fifty-two MDD patients were randomly assigned to either 10-week iCBT (n = 26) or monitored attention control (MAC, n = 26) programs. All patients completed pre- and post-treatment assessments of anhedonia (Snaith–Hamilton Pleasure Scale; SHAPS) and reward circuit reactivity [monetary incentive delay (MID) task during functional magnetic resonance imaging (fMRI)]. Healthy control participants (n = 42) also underwent two fMRI scans while completing the MID task 10 weeks apart.
Results
Both iCBT and MAC groups exhibited a reduction in anhedonia severity post-treatment. Nevertheless, only the iCBT group exhibited enhanced nucleus accumbens (Nacc) and subgenual anterior cingulate cortex (sgACC) activation and functional connectivity from pre- to post-treatment in response to reward feedback. Enhanced Nacc and sgACC activations were associated with reduced anhedonia severity following iCBT treatment, with enhanced Nacc activation also mediating the reduction in anhedonia severity post-treatment.
Conclusions
These findings suggest that increased reward circuit reactivity may contribute to a reduction in anhedonia severity following iCBT treatment for depression.
Optical parametric chirped-pulse amplification implemented using multikilojoule Nd:glass pump lasers is a promising approach for producing ultra-intense pulses (>1023 W/cm2). We report on the MTW-OPAL Laser System, an optical parametric amplifier line (OPAL) pumped by the Nd:doped portion of the multi-terawatt (MTW) laser. This midscale prototype was designed to produce 0.5-PW pulses with technologies scalable to tens of petawatts. Technology choices made for MTW-OPAL were guided by the longer-term goal of two full-scale OPALs pumped by the OMEGA EP to produce 2 × 25-PW beams that would be co-located with kilojoule−nanosecond ultraviolet beams. Several MTW-OPAL campaigns that have been completed since “first light” in March 2020 show that the laser design is fundamentally sound, and optimization continues as we prepare for “first-focus” campaigns later this year.
Concerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings.
Methods
A total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics.
Results
A few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84–0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85–0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52–0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55–0.79).
Conclusions
In pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
Online learning has become an increasingly expected and popular component for education of the modern-day adult learner, including the medical provider. In light of the recent coronavirus pandemic, there has never been more urgency to establish opportunities for supplemental online learning. Heart University aims to be “the go-to online resource” for e-learning in CHD and paediatric-acquired heart disease. It is a carefully curated open access library of paedagogical material for all providers of care to children and adults with CHD or children with acquired heart disease, whether a trainee or a practising provider. In this manuscript, we review the aims, development, current offerings and standing, and future goals of Heart University.
Optical parametric chirped-pulse amplification (OPCPA) [Dubietis et al., Opt. Commun. 88, 437 (1992)] implemented by multikilojoule Nd:glass pump lasers is a promising approach to produce ultraintense pulses (${>}10^{23}~\text{W}/\text{cm}^{2}$). Technologies are being developed to upgrade the OMEGA EP Laser System with the goal to pump an optical parametric amplifier line (EP OPAL) with two of the OMEGA EP beamlines. The resulting ultraintense pulses (1.5 kJ, 20 fs, $10^{24}~\text{W}/\text{cm}^{2}$) would be used jointly with picosecond and nanosecond pulses produced by the other two beamlines. A midscale OPAL pumped by the Multi-Terawatt (MTW) laser is being constructed to produce 7.5-J, 15-fs pulses and demonstrate scalable technologies suitable for the upgrade. MTW OPAL will share a target area with the MTW laser (50 J, 1 to 100 ps), enabling several joint-shot configurations. We report on the status of the MTW OPAL system, and the technology development required for this class of all-OPCPA laser system for ultraintense pulses.
A multi-marker nuclear genotyping approach was performed on larval and adult specimens of Anisakis spp. (N = 689) collected from fish and cetaceans in allopatric and sympatric areas of the two species Anisakis pegreffii and Anisakis simplex (s. s.), in order to: (1) identify specimens belonging to the parental taxa by using nuclear markers (allozymes loci) and sequence analysis of a new diagnostic nuclear DNA locus (i.e. partial sequence of the EF1 α−1 nDNA region) and (2) recognize hybrid categories. According to the Bayesian clustering algorithms, based on those markers, most of the individuals (N = 678) were identified as the parental species [i.e. A. pegreffii or A. simplex (s. s.)], whereas a smaller portion (N = 11) were recognized as F1 hybrids. Discordant results were obtained when using the polymerase chain reaction–restriction fragment length polymorphisms (PCR–RFLPs) of the internal transcribed spacer (ITS) ribosomal DNA (rDNA) on the same specimens, which indicated the occurrence of a large number of ‘hybrids’ both in sympatry and allopatry. These findings raise the question of possible misidentification of specimens belonging to the two parental Anisakis and their hybrid categories derived from the application of that single marker (i.e. PCR–RFLPs analysis of the ITS of rDNA). Finally, Bayesian clustering, using allozymes and EF1 α−1 nDNA markers, has demonstrated that hybridization between A. pegreffii and A. simplex (s. s.) is a contemporary phenomenon in sympatric areas, while no introgressive hybridization takes place between the two species.
The contribution of subsidized food commodities to total food consumption is unknown. We estimated the proportion of individual energy intake from food commodities receiving the largest subsidies from 1995 to 2010 (corn, soyabeans, wheat, rice, sorghum, dairy and livestock).
Design
Integrating information from three federal databases (MyPyramid Equivalents, Food Intakes Converted to Retail Commodities, and What We Eat in America) with data from the 2001–2006 National Health and Nutrition Examination Surveys, we computed a Subsidy Score representing the percentage of total energy intake from subsidized commodities. We examined the score’s distribution and the probability of having a ‘high’ (≥70th percentile) v. ‘low’ (≤30th percentile) score, across the population and subgroups, using multivariate logistic regression.
Setting
Community-dwelling adults in the USA.
Subjects
Participants (n 11 811) aged 18–64 years.
Results
Median Subsidy Score was 56·7 % (interquartile range 47·2–65·4 %). Younger, less educated, poorer, and Mexican Americans had higher scores. After controlling for covariates, age, education and income remained independently associated with the score: compared with individuals aged 55–64 years, individuals aged 18–24 years had a 50 % higher probability of having a high score (P<0·0001). Individuals reporting less than high-school education had 21 % higher probability of having a high score than individuals reporting college completion or higher (P=0·003); individuals in the lowest tertile of income had an 11 % higher probability of having a high score compared with individuals in the highest tertile (P=0·02).
Conclusions
Over 50 % of energy in US diets is derived from federally subsidized commodities.
Depression is characterized by poor executive function, but – counterintuitively – in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study.
Method
One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials).
Results
Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = −0.28, p = 0.007).
Conclusions
Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.
Studies investigating structural brain abnormalities in depression have typically employed a categorical rather than dimensional approach to depression [i.e. comparing subjects with Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined major depressive disorder (MDD) v. healthy controls]. The National Institute of Mental Health, through their Research Domain Criteria initiative, has encouraged a dimensional approach to the study of psychopathology as opposed to an over-reliance on categorical (e.g. DSM-based) diagnostic approaches. Moreover, subthreshold levels of depressive symptoms (i.e. severity levels below DSM criteria) have been found to be associated with a range of negative outcomes, yet have been relatively neglected in neuroimaging research.
Method
To examine the extent to which depressive symptoms – even at subclinical levels – are linearly related to gray matter volume reductions in theoretically important brain regions, we employed whole-brain voxel-based morphometry in a sample of 54 participants.
Results
The severity of mild depressive symptoms, even in a subclinical population, was associated with reduced gray matter volume in the orbitofrontal cortex, anterior cingulate, thalamus, superior temporal gyrus/temporal pole and superior frontal gyrus. A conjunction analysis revealed concordance across two separate measures of depression.
Conclusions
Reduced gray matter volume in theoretically important brain regions can be observed even in a sample that does not meet DSM criteria for MDD, but who nevertheless report relatively elevated levels of depressive symptoms. Overall, these findings highlight the need for additional research using dimensional conceptual and analytic approaches, as well as further investigation of subclinical populations.
The UK has seen a significant transition from Defined Benefit (“DB”) to Defined Contribution (“DC”) for occupational pension saving. The planned automatic enrolment program starting in 2012 is expected to increase the use of DC. The main features of DC are that investment risk falls onto the individual during the pre-retirement phase and that there are no guarantees as to investment returns or the level of pension. In July 2012, Steve Webb, the Pensions Minister, challenged industry to think hard about meeting the need for more certainty about pension savings in DC plans and to consider providing an affordable ‘Money Safe’ guarantee where the member would get back at least the nominal value of their contributions (individual, employer and tax relief). This paper explores whether this is viable for the mass market.
Irradiated cercariae, irradiated schistosomula, or hcterologous infections were used to vaccinate sheep against Schistosoma mattheei infection. In the first experiment four doses of I04 S. mattheei cercariae irradiated at 6Kr were administered to sheep by percutaneous infection at 4 week intervals. This induced a 74% reduction in a challenge infection compared to control sheep while only 13% protection was achieved in a third group of sheep immunised with normal cercariae of the heterologous parasite S. mansoni. No significant differences were seen in histopathology of the liver of any of the sheep but the pathological changes were more severe in the large and small intestines of sheep vaccinated with the heterologous parasite. In the second experiment with irradiated cercariae only one or two immunising exposures were used. The degree of protection in the adult worm load (9–11%) was not significant and no significant differences were noticed in the pathology of the vaccinated and control animals. In the third experiment four doses of irradiated organisms were used to vaccinate five groups of sheep: 3Kr or 6Kr cercariae were administered by percutaneous infection; 6Kr skin-transformed scbistosomula were administered by intramuscular injection; the same 6Kr skin-transformed schistosomula were given by intravenous injection and 6Kr syringe transformed schistosomula were administered by intramuscular injection. The degree of protection (determined as the reduction in worm burden) achieved by these different procedures was respectively 72%, 61%, 77%, 56% and 78%. These results indicate the possibility of making a live vaccine against ovine schistosomiasis and show that effective immunisation is not dependent on the presence of a mature worm infection or on cercarial penetration of the skin by the immunising infection.
1. When mice are infected intraperitoneally with Langat virus only a small proportion develop clinical encephalitis, but all mice have substantial titres of virus in the brain and also incontrovertible histological evidence of encephalitis.
2. When specific antibody is given intraperitoneally or intravenously to mice during the first 3 days after intraperitoneal infection with Langat virus, the viraemia (normally maximal during this period) is depressed, the production of antibody is depressed or delayed, and the incidence of clinical encephalomyelitis is increased significantly.
3. Specific antibody given intraperitoneally or intracerebrally before infection, protects the animals from encephalitis.
4. These findings are discussed in terms of the histology of the central nervous system of the affected mice.
We are very grateful to Miss S. J. Illavia, B.Sc., and to Miss G. E. Fairbairn for their skilled technical assistance; and to Mr S. Peto of the Microbiological Research Establishment for statistical advice.
This work was made possible by a generous grant from the Wellcome Trust and the Endowment Funds of St Thomas's Hospital
1. Irradiation in a whole body dose of 200 rads or more increased the sensitivity of mice to intraperitoneal infection with Langat virus so that the LD 50 was increased to about the intracerebral LD 50.
2. In mice given 500 rads before infection: (a) viraemia was prolonged by about 5 days; (b) the IgM response was depressed; (c) the IgG response was delayed by about 3 days and depressed in titre; (d) virus concentration in the brain rose continuously until death on about the tenth day while in the controls it reached a peak on the fifth day then subsided; (e) histological changes in the CNS were delayed and minimal even at death; (f) irradiated mice died with little evidence of paralysis while the controls died with severe paralysis.
3. In irradiated mice, protection was observed when antibody was administered on the third day following infection. Antibody given on the 3 days after infection to control mice aggravated the disease.
4. The results in this and the preceding paper are discussed in relation to the pathogenesis of encephalitis. It is concluded that neuronal damage is caused both by virus multiplication in neurones and by damage superimposed by inflammatory changes with associated oedema and hypoxia. The inflammatory changes appear to be due to an allergic reaction to virus-antibody complexes formed in the circulation and in the central nervous system.
We are grateful to Miss S. J. Illavia, B.Sc., and Miss G. E. Fairbairn for their skilled technical assistance; to the Department of Radiotherapy at St Thomas's Hospital for providing time and staff to help with the irradiation experiments; and to Mr S. Peto of the Microbiological Research Establishment for statistical advice.
This work was made possible by a generous grant from the Wellcome Trust and the Endowment Funds of St Thomas's Hospital.
In field experiments carried out over a period of three years studies were made of the effects on soil moisture characteristics and crop yields of incorporating pulverized fuel ash into the surface 30 cm of a sandy loam and a coarse sand. Ash from two different sources was used at rates equivalent to 0, 125, 251, 502 and 753 t/ha and crops of carrots, lettuce, radish and red beet were grown.
On every occasion when determinations were made the available-water capacities of the soils treated with 251 t/ha or more of ash were greater than the untreated soils; the largest increase (93%) was obtained with the highest rate of ash. Moisture release characteristics indicated that the increased amount of available water was retained in the soils at matric suctions between 0·05 and 1·0 atmospheres.
Despite the increased amount of available water retained in these soils there was generally no beneficial effect on crop growth and yields.
This review includes a brief discussion, from the perspective of the pediatric cardiologist, of the rationale for creation and maintenance of multi-institutional databases of outcomes of the treatment of patients with congenital and paediatric cardiac disease, together with a history of the evolution of such databases, and a description of the current state of the art. A number of projects designed to have broad-based impact are currently in the design phase, or have already been implemented. Not surprisingly, most of the efforts thus far have focused on catheterization procedures and interventions, although some work examining other aspects of paediatric cardiology practice is also beginning. This review briefly describes several European and North American initiatives related to databases for pediatric and congenital cardiology including the Central Cardiac Audit Database of the United Kingdom, national database initiatives for pediatric cardiology in Switzerland and Germany, various database initiatives under the leadership of the Working Groups of The Association for European Paediatric Cardiology, the IMPACT Registry™ (IMproving Pediatric and Adult Congenital Treatment) of the National Cardiovascular Data Registry® of The American College of Cardiology Foundation® and The Society for Cardiovascular Angiography and Interventions (SCAI), the Mid-Atlantic Group of Interventional Cardiology (MAGIC) Catheterization Outcomes Project, the Congenital Cardiac Catheterization Project on Outcomes (C3PO), the Congenital Cardiovascular Interventional Study Consortium (CCISC), and the Joint Council on Congenital Heart Disease (JCCHD) National Quality Improvement Initiative. These projects, each leveraging multicentre data and collaboration, demonstrate the enormous progress that has occurred over the last several years to improve the quality and consistency of information about nonsurgical treatment for congenital cardiac disease. The paediatric cardiology field is well-poised to move quickly beyond outcome assessment and benchmarking, to collaborative quality improvement.